National recognition by external sources such as U.S. News & World Report comes as no surprise to the thousands who pass through Connecticut Children’s Medical Center each year.

What may be unexpected to those patients is that such success is the fruit of a more than 50-year legacy of the pediatric department at UConn School of Medicine advancing pediatric medicine, research, and education in Connecticut — and putting the health of the state’s tiniest residents first.

The life-changing work done by UConn’s Department of Pediatrics is made possible by a special partnership: Connecticut Children’s Medical Center is the teaching hospital where medical students, pediatric residents, and fellows are trained, as well as the home of the faculty’s clinical care work.

“UConn’s Department of Pediatrics’ strong relationship with Connecticut Children’s is excellent and seamless. There is no us and them. We are truly one, and we couldn’t excel without each other,” says Dr. Bruce T. Liang, the dean of the UConn School of Medicine since 2015. Liang has helped expand the two institutions’ joint recruitment of world-renowned physician-scientists and has led much of their growth in pediatric research.

For the Greater Good

The seeds of excellence in pediatric care in the Hartford area were planted in 1967 with the founding of UConn’s Department of Pediatrics, shortly before the medical school admitted its first class in 1968. UConn John Dempsey Hospital offered pediatric hospital care when it opened in 1975. Hartford-area hospitals had an informal agreement not to duplicate pediatric specialty services — patients were transferred among the hospitals based on their specialty care needs.

Connecticut Children’s was born in April 1996 after Newington Children’s Hospital, Hartford Hospital, and John Dempsey voluntarily closed their pediatric services so a comprehensive children’s hospital could open. It was established by state legislation and a 99-year lease of land on Hartford Hospital’s campus for 1 dollar per year. St. Francis Hospital and Medical Center’s pediatric programs were also incorporated. Uniquely, the leadership structure of the new pediatric hospital required that the same individual serve as both UConn’s Department of Pediatrics chair and Connecticut Children’s physician-in-chief.

“I am honored to have seen firsthand the strong evolution in pediatrics since my 1980s UConn pediatric residency training,” says Dr. Juan C. Salazar, who has served in that joint leadership role at UConn and Connecticut Children’s since 2013. “It is amazing that the strengths of four different Hartford hospitals came together for the greater good of our children and continue to offer the best pediatric care. It’s been an incredible success, allowing us to grow pediatrics clinically and educationally, along with our research mission.”

Salazar cites pediatric endocrinologists Dr. David Weinstein and Dr. Emily Germain-Lee as “two of several perfect examples of how the partnership of Connecticut Children’s and UConn really works seamlessly, with clinical services provided at Connecticut Children’s while robust laboratory research and clinical trials are under way at UConn.”

For 2018–19, U.S. News & World Report ranks Connecticut Children’s among the best hospitals in four pediatric specialties: cardiology and heart surgery, diabetes and endocrinology, neonatology, and urology. As one of the state’s largest care providers with 300 faculty members, UConn’s Department of Pediatrics has 31 medical and 13 surgical specialties.

Dr. David Weinstein with a patient Peter Morenus

For a Brighter Future

In addition to translational research and top clinical care, UConn Health’s mission includes a third focus on teaching the practitioners of tomorrow. UConn is the largest educator for the state’s pediatric medicine workforce, as up to 60 percent of pediatricians in Connecticut have graduated from UConn’s medical school or its pediatric training programs.

Historically, UConn has also provided the largest pipeline of medical students into the state’s pediatric residency programs — each year up to 20 percent of UConn’s graduating medical school class chooses to specialize in pediatrics, entering residency training programs here or around the country.

“Along with research advancements, our significant focus is the education and training of our next generation of pediatricians and pediatric specialists, many of whom stay right here in Connecticut to serve the state,” says Liang.

UConn and Connecticut Children’s continue to strengthen their partnership in all three areas by building relationships with other organizations.

The two institutions in 2016 joined with another collaborator, The Jackson Laboratory (JAX) for Genomic Medicine located on UConn Health’s campus, to recruit Dr. Ching C. Lau, an internationally recognized pediatric brain and bone tumor clinician and researcher.

UConn and Connecticut Children’s look forward to growing their alliance, Liang says, and are planning joint physician-scientist recruitments in the fields of medical genetics and gastroenterology, as well as further collaborations in maternal-fetal medicine.

World-renowned physician-scientists across specialties bring to life the vision of Connecticut Children’s Medical Center and UConn School of Medicine’s Department of Pediatrics. Read on to learn about three of the groundbreaking physician-scientists who are currently dedicated to improving the lives of children in Connecticut and around the world.

A Vision for the Future of Pediatric Cancer

In 2016, Connecticut Children’s and UConn joined with another collaborator, The Jackson Laboratory (JAX) for Genomic Medicine located on UConn Health’s campus, to recruit Dr. Ching C. Lau, an internationally recognized pediatric brain and bone tumor clinician and researcher, from Texas Children’s Hospital in Houston.

As medical director of hematology-oncology at Connecticut Children’s and head of the Division of Pediatric Hematology-Oncology in the Department of Pediatrics at UConn, Lau’s JAX-based laboratory aims to leverage new, sophisticated genomic medicine techniques, mouse models, and therapeutic treatments to choose the best therapy for patients and discover new treatments.

When he was awarded the inaugural Martin J. Gavin Endowed Chair in Hematology/Oncology at Connecticut Children’s, Lau said he was attracted to the vision and dedication of Connecticut Children’s Medical Center.

“I dream that one day when I look at a child diagnosed with cancer, I can look him or her in the eye and say, ‘You will be cured without having to come to the hospital for therapy. You just have to go home and take this medicine,’” he said.

Lau is focused on accelerating the pace and success rate of clinical trials in pediatric cancer patients. “Although the incidence of cancer among children is much lower than that in adults,” he says, “it can be just as deadly. And because of the smaller number of patients available, clinical trials of new treatments for pediatric cancers are conducted at a much slower pace. Typically patients are enrolled in clinical trials after their cancers progress or are found not to be responsive to standard therapy.”
As a result, he says, pediatric cancer patients are exposed to side effects of standard therapy without therapeutic benefit. “This is a particularly serious problem for children because they are still undergoing normal growth and are particularly vulnerable to the side effects of anticancer drugs.”

By using the combined approach of genomic medicine and accurate mouse models to choose the best therapy for each patient, Lau hopes to improve the speed and outcome of clinical trials as well as to reduce unnecessary side effects for children with cancer.

One way he’s speeding up the process is through Smash Childhood Cancer, an initiative he’s spearheading for the U.S. alongside international researchers and IBM to find prospective treatments for childhood cancers by conducting millions of virtual experiments to help pinpoint promising drug candidates for further study using IBM’s World Community Grid.

“This kind of research expedites finding new treatments for childhood cancers,” Lau says. “Crowdsourcing computer processing power enables us to perform millions of experiments virtually and will save us years of experiments. It is bringing us that much closer to finding the right drug for each type of cancer.”

Administering New Therapy — and Hope

In late July, a patient named Jerrod received a drug infusion that he’s been waiting for his entire life.

Jerrod was the first patient to receive a promising investigational gene therapy to treat glycogen storage disease type Ia, the rare, potentially deadly genetic disorder he was born with. Dr. David Weinstein, a world-renowned pediatric endocrinologist and director of the Glycogen Storage Disease Program at Connecticut Children’s Medical Center and UConn Health, has been working to develop the treatment for two decades and calls the trial “a big leap forward for GSD.”

Healthy livers store excess sugar from food and release it into our bloodstreams when we need it as processed sugar enzymes called glycogen. However, in the seven forms of GSD, the liver fails to break down glycogen into glucose, causing the body’s blood sugar levels to drop dangerously low, which can lead to seizure or death. Patients stay alive by consuming a cornstarch mixture every few hours to keep their blood sugar up.

The gene therapy undergoing the Phase 1/2 clinical trial, approved by the FDA in April, delivers a new copy of the gene to the patient’s liver to replace deficient sugar enzymes and jumpstart the body’s glucose control. Studies in animal models have already shown the promising gene therapy to be safe, effective, and long-lasting.

The clinical trial is in conjunction with the biopharmaceutical company Ultragenyx and will soon expand from UConn Health in the U.S. to other sites including Canada, Spain, and the Netherlands.

“This gene therapy is hope for all us GSD patients,” says Jerrod, who asked that his last name be withheld. “We are all extremely excited. Dr. Weinstein is a savior and so is the entire GSD program.”

Weinstein moved his GSD program — the largest in the world — to Connecticut Children’s and UConn Health in early 2017. His multidisciplinary team cares for 600 patients from 48 countries.

“The strong synergies and collaborative team science happening at UConn and Connecticut Children’s are world class and the most fertile ground to make a GSD cure reality,” says Weinstein.

Writing the Rulebook

Dr. Emily Germain-Lee, a professor of pediatrics and chief of pediatric endocrinology and diabetes, moved her first-of-its-kind Albright Center from Johns Hopkins School of Medicine and Kennedy Krieger Institute to UConn and Connecticut Children’s in October 2016. She has cared for more patients who have a specific rare set of endocrine diseases than any other doctor in the world.

“She has redefined the field of pediatric endocrinology,” Salazar said when the hire was announced. “Patients and families travel from all over the world seeking Dr. Germain-Lee’s care.”

Germain-Lee’s patients suffer from pseudohypoparathyroidism and its related disorders, including Albright hereditary osteodystrophy (AHO), a rare inherited bone disorder caused by a genetic mutation that often leads to short bones and short stature. It is also frequently accompanied by severe multihormonal dysfunction in the body.

This summer, Germain-Lee co-authored the first international guidelines to help doctors around the globe diagnose and manage patients with the diseases. The new guidelines call for human growth hormone treatment for the vast majority of the patients who are at risk for short stature due to growth hormone deficiency. Germain-Lee was the first to discover that part of the reason why AHO patients are short is that two-thirds of them have a growth hormone deficiency.

Her long-term global clinical trial studies have shown the promising benefits of growth hormone treatment, including its ability to drastically increase a patient’s short stature to their original destined height potential while also improving their lipid levels and reducing obesity. With her research in the final stages, Germain-Lee is working toward gaining FDA approval of the therapy, which would be the first new therapy for the disorder in 70 years.

“I am thrilled to be a part of the combined power of UConn School of Medicine and Connecticut Children’s Medical Center for advancing children’s health and discovering new treatments of disease through research,” says Germain-Lee.

Research doesn’t stop when we report it. Here are updates on past UConn Health Journal stories:

Glycogen Storage Disease

The world’s first gene therapy clinical trial for Glycogen Storage Disease (GSD) Type Ia is expected to start this year, hosted by the GSD Program at Connecticut Children’s Medical Center and UConn Health, under the direction of Dr. David Weinstein. The FDA–approved trials will be done in conjunction with biopharmaceutical company Ultragenyx.

Advancing Surgical Care for Older Adults

UConn John Dempsey Hospital will be one of seven U.S. hospitals to pilot-test newly developed guidelines for improving the quality of surgical care for older adults for the American College of Surgeons’ Coalition for Quality in Geriatric Surgery (CQGS), the American Geriatric Society, and the John A. Hartford Foundation.

Detecting Hearing Loss

Findings presented at the 53rd American Neurotology Society annual spring meeting reveal the first potential biomarker for noise-induced hearing loss. A collaborative study by UConn Health and Sensorion showed changing levels of prestin, an outer hair cell protein, in the blood correlated with the severity of hearing loss.

Breast Health

UConn Health assistant professor and breast surgeon Dr. Christina Stevenson has begun providing breast health education in hair salons, funded by the Connecticut Breast Health Initiative. The program aims to reach women in Hartford County who may be at risk for late- stage diagnosis of breast cancer due to health care access barriers.

Skin Cancer Screening

Up to 60 percent of UConn Health patients with a suspicious skin lesion or mole can now avoid invasive biopsies thanks to confocal microscopy technology, according to dermatologist Dr. Jane Grant-Kels. The technology uses a painless laser light to see skin cells on a cellular level and help doctors identify skin cancers, including melanoma.

Cooling Cap Therapy

Marisa Dolce, a Carole and Ray Neag Comprehensive Cancer Center breast cancer patient, reported keeping 70 percent of her hair as the first UConn Health patient to use optional scalp-cooling technology while undergoing chemotherapy. UConn Health is the only Connecticut institution outside Fairfield County to offer the FDA-approved DigniCap.

Two years ago, we published the first UConn Health Journal with the goal of giving physicians, dentists, and the public insight into the groundbreaking research and life-changing clinical care happening at UConn Health. As an academic medical center, UConn Health makes the discoveries that shape the future of health care. Our scientists work to understand medicine’s biggest mysteries, design new therapies and treatments, and turn laboratory breakthroughs into advances in patient care.

As our team collaborates to produce each issue, I constantly find myself in awe of everything that drives UConn Health’s innovations. Our stories can be heavy on science or heavy on heart, sometimes in the same issue. This spring, the story “Aches, Age, and Influenza” told of how UConn scientists’ findings in mice may help us prevent influenza-related muscle deterioration in the elderly. In the same edition, we got to know 11-year-old Alyssa Temkin, who since birth has struggled with an unforgiving, deadly disease for which a new UConn doctor is closing in on a cure.

Most of the time, though, our stories walk the line between the two. Because when it comes down to it, these advancements are based on science. But by definition, medical discoveries always impact real people. The mission of UConn Health Journal, like that of the UConn Health enterprise, is to translate that research: What does it mean for you? For your patients? For your loved ones?

In this issue, we’re exploring one topic from several angles. The brain has for centuries fascinated and perplexed. The more we learn about it, the more we find there is left to discover. At UConn, those who work with the brain range from a neurologist with a ringside seat to the evolution of concussion treatment to a radiologist and medical physicist who harnessed 3-D printing technology to give surgeons a practice brain for complicated procedures.

And please, let us know what you think and what else you’d like to read about. Email me anytime at julie.bartucca@uconn.edu.

For patients and their families who live with Glycogen Storage Disease, a new gene therapy nearing clinical trial at UConn Health will mean freedom from the constant countdown to the next dose of medication.

By Julie Bartucca Photography by Peter Morenus

Alyssa Temkin, 11, takes a break during a basketball game to drink Tolerex, the special formula that keeps her blood sugar from crashing to dangerously low levels. Alyssa has Glycogen Storage Disease and must drink the formula every 90 minutes to stay alive. Photo: Peter Morenus

Imagine never being able to hit the snooze button or oversleep, never being able to cheat on your diet or fall asleep in front of the TV because it could mean life or death — for you, or worse, your child.

That’s what the 1 in 100,000 people worldwide with Glycogen Storage Disease (GSD), a genetic liver disorder — and their parents — live with every day.

Dr. David Weinstein, who in January moved his world-renowned GSD program from the University of Florida to UConn Health and Connecticut Children’s Medical Center, has dedicated his life to giving these families hope. Although a life-saving treatment was discovered in the 1970s — taking a cornstarch mixture every few hours — research had halted for decades after that. And today, patients are still slaves to the clock; the effects of cornstarch last only a few hours, and even an extended-release form has its pitfalls.

But soon, that could change. Weinstein and his team are on the verge of testing in a human clinical trial the first GSD gene therapy, which has worked for canines and mice with the illness.

For the patients and their families who live in a constant countdown to the next feeding, the new therapy would mean freedom. A normal life, where mistakes can be made. Where they no longer have to be perfect.

There was no research going on anywhere in the world in this disease. And if there’s no research, that means there’s no hope.

— Dr. David Weinstein

Fatal Mistakes

Healthy livers store excess sugar from food and release it into our bloodstreams when we need it, as processed sugar enzymes called glycogen. However, in the seven forms of GSD, the liver fails to break down glycogen into glucose, causing the body’s blood sugar levels to drop dangerously low, which can lead to seizure or death.

The discovery of cornstarch therapy was a huge turning point, but it wasn’t enough.

“The problem with this disease is that people need cornstarch every four hours. People have died because their parents overslept,” says Weinstein. One missed alarm and a patient could die. A malfunctioning piece of medical equipment could mean a dangerous seizure.

“One of the parents was giving a talk recently and said, ‘Do you know what it’s like to have to be perfect all the time?’” Weinstein says. “And that’s what these families live with. It’s extreme stress.”

Weinstein and his team have made great strides. GSD was once considered a childhood disease — this generation is the first to survive to adulthood. Now, patients are doctors, athletes, mothers — more than 50 babies have been born to mothers with GSD since the first in 2003. But they still live under constant pressure. The disease is relentless, unforgiving.

For the patients and their families who live in a constant countdown to the next feeding, the new therapy would mean freedom. A normal life, where mistakes can be made. Where they no longer have to be perfect.

The Temkin family of West Hartford knows all too well what can happen.

When Gayle and Steve Temkin brought baby Alyssa home from the hospital at three days old, Gayle knew something was wrong with her daughter. By the time they got to a hospital that night, Alyssa was in full liver and renal failure. Her sugars were undetectable. Without intervention, she wouldn’t survive an hour, doctors said.

It was six months, several hospitals, countless invasive tests, and second and third opinions before Alyssa was diagnosed with GSD at Mount Sinai Hospital in New York City.

Alyssa is now 11, a smiling, soft-spoken sixth-grader who enjoys playing sports, acts in plays, and is learning to play guitar and dance. She gets good grades and loves her friends. But every 90 minutes, every single day, she must check her blood sugar and drink Tolerex, a special formula that keeps her sugar up. Alyssa is the only known GSD patient who can’t tolerate cornstarch, and Tolerex doesn’t last as long, so the time between her feedings is even shorter than it is for most GSD patients.

While the Temkins do everything they can to make Alyssa’s life normal, there are constant reminders that it is anything but.

Gayle spends every day at Alyssa’s school. For years, she would go into the classroom to feed Alyssa, first through a feeding tube and, more recently, with a drinkable formula. This year, Alyssa has gained some freedom. An Apple Watch reminds her when it’s time to test her blood and drink, and she reports her sugar level to her mom via a walkie talkie. Gayle, a former social worker, stays close, just in case.

If Alyssa’s sugar gets too low, she doesn’t feel it. Unlike most people, GSD patients don’t feel shaky or get headaches when their sugar drops — at least not until it’s too late. By then, they could be moments from having a seizure.

In 2015, Alyssa suffered a near-fatal seizure after the pump that feeds her dextrose through the night failed. “There is nothing about this disease that’s forgiving,” says Gayle. “It doesn’t matter what regimen you’re on; it could be a bad batch of something — We think we’re doing everything right, and the pump malfunctions.”

Dr. David Weinstein, head of the Glycogen Storage Disease Program at UConn Health and Connecticut Children’s Medical Center, walks with Alyssa Temkin through the new clinic at Connecticut Children’s. Weinstein has treated Alyssa since she was diagnosed with GSD at 6 months old. Her family and other Hartford-area philanthropists supported the move of Weinstein’s program from Florida to Connecticut. Photo: Peter Morenus

No Research, No Hope

Weinstein had no intention of dedicating his life to curing GSD. As a young physician at Boston Children’s Hospital specializing in sugar disorders in 1998, Weinstein was caring for just two patients with GSD when he was invited to a national conference of the Association for Glycogen Storage Disease.

“I showed up at this meeting and was shocked by what I saw,” he says. The conference started with a moment of silence and a reading of the names of all the children who had died from GSD that year. The research presented was decades old. And the only treatment option being discussed was liver transplantation to combat complications from the disorder.

“There was no research going on anywhere in the world in this disease,” Weinstein says. “And if there’s no research, that means there’s no hope.”

A conversation with a mother there changed the course of Weinstein’s life. Knowing no one at the conference, he sat down for lunch next to Kathy Dahlberg, who had one-year-old twin sons already on the liver transplant list. She told Weinstein how sick her children were, and that her only hope was that they’d live long enough to get their liver transplants.

“Over lunch at that conference, I decided that somebody had to care about these children. The children shouldn’t have to suffer just because it was a rare disease,” Weinstein says. “The world didn’t need another diabetes doctor. This is where I could make a difference.”

Gayle Temkin talks to her daughter Alyssa in a school stairwell. Gayle attends school with Alyssa every day, waiting in a room off the main office for Alyssa to check in via walkie talkie every 90 minutes to report her blood sugar level and that she’s drunk her Tolerex. GSD patients don’t feel the signs of low sugar until they are moments from a seizure, so Gayle stays close around the clock. Photo: Peter Morenus

As soon as he returned to Boston, Weinstein shifted his research focus to GSD and built the program there before moving it to the University of Florida in 2005 in order to work with the veterinary program. He has successfully treated dogs with his gene therapy, turning a fatal disease into one where dogs born with GSD are thriving.

Today, Weinstein sees 500 patients from 49 states and 45 countries. With help from Alyssa’s Angel Fund — started by the Temkins when Alyssa was a baby — and other charities, he has established centers all over the world.

All the Way

In January, the GSD lab moved to UConn Health’s Farmington campus. At the same time, a clinical and research unit supported financially by the Temkins and other local philanthropists opened at Connecticut Children’s. Gayle Temkin, Alan Lazowski, and Barry Stein are the trustees for the Global Center for Glycogen Storage Disease, and through the new organization will continue to raise money to support Weinstein’s program. They are working to set up other forms of assistance for patients and their families, including a closet with free supplies at the clinic, and support programs for families once the clinical trials start.

Because GSD patients are now surviving well into adulthood, the partnership between the two institutions makes great sense. “We’re much stronger working together,” Weinstein says.

Although Weinstein is the only doctor in the world dedicated to curing GSD, he says he’s not doing it alone — far from it.

“I’ve never seen a program like ours. I only do one disease. Everybody on my team does just one disease,” he says. “This is personal. Most people have a connection to the condition, and so they’ll work until everything’s done. It’s just a dedication that I’ve never experienced anyplace else.”

The bulk of Weinstein’s Florida team came to Connecticut with him. His team includes GSD patients and parents, including several who have called him out of the blue to tell him all they want is to work with him. One, who moved to Connecticut from Minnesota to join the new center, is Kathy Dahlberg, the mother who changed Weinstein’s course all those years ago. Her twins are now sophomores in college.

And, after nearly two decades of dedicated research, Weinstein’s next step is the one he’s been working toward all along. Human safety trials of his gene therapy, in conjunction with Dimension Therapeutics out of Cambridge, Mass., are expected to start this year. UConn will coordinate the trials with collaborating centers all over the world. Full-treatment trials should start in 2020.

The ultimate goal for the gene therapy, according to Weinstein,
is to prevent low blood sugars, eliminate the dependence on cornstarch, and give patients normal lives where oversleeping isn’t the worst-case scenario.

“If we can accomplish that, we’ve come all the way,” he says.

“The cure is right at our fingertips. He knew he could do this,” says Gayle. “When we first brought Alyssa to him, he said, ‘By her Bat Mitzvah, by the time she’s 12 or 13, we should be able to cure her.’ And she’s 11.